Efficacy and clinical safety of pegbovigrastim for preventing naturally occurring clinical mastitis in periparturient primiparous and multiparous cows on US commercial dairies

Abstract

Periparturient dairy cows experience impaired immune function, exhibited as a transient decrease in neutrophil function. This decrease in immune competence is associated with an increase in susceptibility to bacterial infections, including mastitis and metritis. Bovine granulocyte colony stimulating factor (bG-CSF) is an endogenous protein that enhances neutrophil bactericidal functions and increases the production of neutrophils from bone marrow precursors. Administration of pegbovigrastim (recombinant bG-CSF covalently bound to polyethylene glycol) around the time of calving has been shown to reduce the incidence of new clinical mastitis cases in a natural disease model system. To further explore the application of pegbovigrastim under herd management systems typical of those found in the US dairy industry, we conducted a multicenter field study to evaluate the efficacy and clinical safety of pegbovigrastim administered to multiparous cows and heifers approximately 7 d before calving and within 24 h of calving. Responses of treated cows were compared with those of animals treated with sterile saline. Animals treated with pegbovigrastim exhibited 4- to 5-fold increases in circulating neutrophil numbers within 24 h of treatment initiation, and this increase persisted at least a week beyond the second dose. Pegbovigrastim-treated animals exhibited a 35% decrease in the incidence of clinical mastitis relative to the controls during the first 30 d of lactation. Animals treated with pegbovigrastim also exhibited a 52% reduction in failure to return to visual estrus within 80 d of calving. We observed no differences in somatic cell count or milk composition between treated and control animals. We also found no differences in the duration of pregnancy or proportion of viable calves in treated cows relative to control animals. These results indicate that administration of pegbovigrastim provides a well-tolerated, novel approach to overcoming periparturient immune suppression, resulting in reduced susceptibility to clinical mastitis during early lactation.

Hematological and biochemical parameters of dairy calves submitted to pegbovigrastim administration

“…The number of total leukocytes and segmented neutrophils in experiment 1 was higher in the IMR group than in the CTR group, reaching a peak at 24 h (d 2) after the administration of pegbovigrastim and decreasing 48 h after (d 3), but nevertheless maintaining a neutrophilia up to 312 h (d 14) after treatment. Similar results were found in peripartum cows receiving pegbovigrastim 7 d before calving and 24 h postpartum, in which neutrophils remained elevated for at least 7 d after the second dose (Canning et al, 2017). These results could justify the use of this drug in newborn calves because it increases the number of circulating cells of innate immunity.…”

“…Recently, a bovine G-CSF was developed through covalent binding of polyethylene glycol (PEG) to G-CSF to increase its lifespan around 7 to 14 d and allow a reduction in first-pass renal clearance and proteolytic degradation (Kehrli et al, 1991;Molineux, 2003). Bovine G-CSF has been shown to significantly increase neutrophil concentration and function in peripartum cows, increase production of milk, and reduce susceptibility to clinical mastitis during lactation (Canning et al, 2017;Ruiz et al, 2017). However, no information is available regarding the effectiveness of the response to PEG bovine G-CSF on calves' immune system and their metabolic profile.…”

Review: Relationships between metabolism and neutrophil function in dairy cows in the peripartum period

“…There were no differences among groups in the severity of cases of mastitis, although the study was not really powered to assess this outcome. Canning et al (2017) randomised a total of 640 cows across four farms to receive either 15 mg PEG-rbG-CSF (equivalent to 22 μg/kg for a 675 kg cow) or saline, twice, as above. They observed increases in circulating neutrophil counts similar to Hassfurther et al (2015) for the corresponding time points and dose.…”

Análise Experimental Do Comportamento Dinâmico De Uma Coluna De Haste De Bombeio Mecânico De Poços De Petróleo Usando Analogia De Movimento De Pêndulos Múltiplos

“…Essa é uma enfermidade multifatorial, caracterizada por uma inflamação na glândula mamária e ocasionada principalmente por agentes infecciosos como bactérias do gênero Staphylococcus spp., Streptococcus spp., Escherichia coli, Corynebacterium spp., Micrococcus spp., Pseudomonas spp, fungos e vírus. A manifestação da mastite é dependente de uma interação entre as condições ambientais, os microrganismos causadores da doença e a ocorrência coordenada das respostas imunes inatas e adquiridas (CANNING et al, 2017). Segundo Lopes et al (2012), o impacto econômico anual da mastite pode variar de 70 a 270 mil reais para frequências médias anuais de 1,7 e 15%, respectivamente, em propriedades leiteiras com 100 animais lactantes.…”